Sex-Based Differences in Interstitial Lung Disease.

Interstitial lung diseases comprise a family of progressive pulmonary disorders that are often idiopathic or associated with various systemic diseases and that is characterized by bilateral lung involvement with inflammation and tissue remodeling or fibrosis. The impact of sex, including the anatomic and physiologic traits that one is born with, on the development and progression of interstitial lung diseases is not entirely clear. Variances between men and women are driven by differences in male and female biology and sex hormones, among other differences, but their role remains uncertain. In this review, we summarize sex-related differences in the epidemiology and progression of certain interstitial lung diseases with a focus on the connective tissue related interstitial lung diseases, idiopathic pulmonary fibrosis, and sarcoidosis. We also discuss cellular and pre-clinical studies that might shed light on the potential mechanisms responsible for these differences in the hope of unveiling potential targets for intervention and stimulating research in this needed field of investigation.

A 54-Year-Old Man With Anasarca, Dyspnea, and Recurrent Bilateral Pleural Effusions.

CASE PRESENTATION: A 54-year-old African-American man presented with 2 years of progressively worsening dyspnea and anasarca. Over the past 6 months he gained 30 lbs with worsening lower extremity, abdominal wall, and scrotal edema. A recent workup for cardiac, renal, and liver disease, including two-dimensional echocardiogram, liver and renal function tests, and abdominal ultrasound, was unremarkable. He reported a 15-pack year history of smoking and quit 3 years ago. Chest radiograph at that time revealed bilateral pleural effusions that were both reportedly milky in appearance when drained by thoracenteses.

Scleroderma-related interstitial lung disease.

Scleroderma-related interstitial lung disease (SSc-ILD) is a pulmonary fibrosing disorder characterized by systemic inflammation and progressive scarring of the lungs that leads to respiratory failure. Although certain immunosuppressive therapies may slow disease progression, current treatment strategies are not curative; consequently, SSc-ILD continues to be a major cause of morbidity and mortality. We present four cases of SSc-ILD that emphasize the importance of early screening and detection, close follow-up, and aggressive management. We also highlight the need for well-conducted clinical trials designed to identify new and effective treatments.

Pulmonary necrobiotic nodules in Crohn's disease: a rare extra-intestinal manifestation.

Pulmonary necrobiotic nodules represent a rare extra-intestinal manifestation of Crohn's disease. Histologically, they are composed of sterile aggregates of inflammatory cells with necrosis. The differential diagnosis is broad, and exclusion of infectious etiologies is mandatory before starting immunosuppressive therapy. Here, we present the fifth reported case of pulmonary necrobiotic nodules in Crohn's disease. Our patient had new-onset Crohn's disease associated with both cavitating and non-cavitating lung nodules that were confirmed to be necrobiotic nodules by biopsy. The patient was started on mesalamine and prednisone, with subsequent improvement of his gastrointestinal symptoms and regression of the necrobiotic nodules.

Pulmonary IgG4+ Rosai-Dorfman disease.

Rosai-Dorfman disease (RDD) is a rare non-malignant proliferation of histiocytes of unknown aetiology that mainly affects lymph nodes. Here we report a case of RDD that presented a diagnostic dilemma due to its atypical presentation and the overlap with IgG4 disease. Our case presented with interstitial lung involvement without lymphadenopathy. Open lung biopsy suggested the diagnosis of RDD. However, the predominant IgG4 positive plasma cells together with the absence of lymphadenopathy were not typical of RDD. Within 1 year, the patient developed diffuse lymphadenopathy and immunohistochemical staining of lymph node aspirates confirmed the diagnosis. Despite trials of corticosteroid therapy, the disease progressed.

Smoking-related interstitial fibrosis (SRIF) and pulmonary hypertension.

Smoking-related interstitial fibrosis (SRIF) is a relatively new term used to describe chronic interstitial fibrosis that can develop in smokers. The association of SRIF with pulmonary hypertension has not been described. We present a 55-year-old man with an extensive smoking history who presented for evaluation of insidious onset of dyspnoea on exertion and hypoxaemic respiratory failure. Physical examination was unremarkable. Pulmonary function testing demonstrated a marked reduction of the diffusion capacity with no obstruction or restriction. Ventilation perfusion scan showed no evidence of thromboembolic disease. High-resolution chest CT revealed minimal biapical pleural parenchymal scarring and subtle dependent atelectasis. Serological markers for connective tissue diseases were negative. Open lung biopsy was consistent with SRIF. Vascular intimal proliferation consistent with pulmonary hypertension was also noted. Right heart catheterisation yielded mild pulmonary hypertension and treatment was initiated with tadalafil and bosentan.

Dyspnoea and the ovaries: a rare presentation of Krukenberg tumour.

Krukenberg tumour is a metastatic signet-ring adenocarcinoma of the ovary, usually with a gastrointestinal primary detected metachronously or synchronously. We present here a case of a 48 year-old woman who presented with a prolonged history of dyspnoea on exertion. Workup had revealed a pelvic mass. Thoracocentesis of her pleural effusion, with cytology, and pathology reports from her total abdominal hysterectomy with bilateral salpingo-oophorectomy revealed a carcinoma with signet-ring cells. Immunostains were positive for CDX2, CK7 and CK20, which was highly suggestive of a gastric primary. Colonoscopy was negative, and an oesophagogastroduodenoscopy revealed a few small crater ulcers, the biopsy of which was negative for cancer. A right-sided pleurodesis was performed for the unremitting malignant effusion, and a PleurX catheter was placed in her left pleural space. She was discharged home with a very poor prognosis.

A case of progressive lung fibrosis.

Idiopathic pulmonary fibrosis is characterized by progressive fibrosis of the lung and poor prognosis. This is the case report of a patient with idiopathic pulmonary fibrosis that highlights many of the controversies inherent in the diagnosis and treatment of this disease.

Management of idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a progressive fibrosing lung disorder characterized by progressive dyspnea, exercise intolerance and, ultimately, respiratory failure and death. The incidence of IPF seems to be increasing, whereas its etiology remains unelucidated. Agents capable of modulating inflammation, kinase pathways, vascular tone, coagulation and fibrosis have been tested in clinical studies although not always in large, randomized, placebo-controlled prospective trials. Despite this effort, a therapy capable of improving survival remains elusive. Consequently, the management of IPF focuses on the early identification of subjects for lung transplantation and on the treatment of comorbidities such as hypoxemia, cough and deconditioning. Until effective therapies are identified, patients and referring physicians are urged to consider participation in well-designed clinical trials.

Bronchoalveolar lavage fluid D dimer levels are higher and more prevalent in black patients with pulmonary sarcoidosis.

BACKGROUND: Abnormalities of lung coagulation and fibrinolysis in sarcoidosis are thought to play a role in the pathogenesis of this disease. OBJECTIVE: We previously showed that bronchoalveolar lavage fluid (BALF) D dimer directly correlated with various measures of severity in sarcoidosis. Here, we analyze our observation that BALF D dimer was more frequently found at higher levels in African-American patients with pulmonary sarcoidosis. METHODS: BALF D dimer was measured in 55 subjects with pulmonary sarcoidosis and 31 healthy volunteers by enzyme immunoassay. The healthy group established a normal range of BALF D dimer with 71 ng/ml as the highest measured level. This was the cut point for comparisons among the patients with sarcoidosis. RESULTS: High BALF D dimer levels (>71 ng/ml) were found in younger patients with sarcoidosis and were associated with a significantly lower percent predicted forced expiratory volume in 1 s and greater numbers of BAL lymphocytes. Black patients with sarcoidosis had higher BALF D dimer levels (median 131, range 0-2,040 ng/ml) than white patients (median 18, range 0-605 ng/ml; p = 0.011). Higher than normal BALF D dimer levels were found in 61% of the black subjects with sarcoidosis, but in only 20% of the white individuals (chi(2) = 5.539, p = 0.019). BALF D dimer was the only disease measure that discriminated black from white individuals with sarcoidosis. CONCLUSION: BALF D dimer is an indicator of lung fibrin formation and degradation in sarcoidosis. The relationship of high D dimer levels with greater BAL lymphocytosis and worse lung function may be a marker of active sarcoidosis, especially in African-Americans who tend to suffer a more serious form of the disease.

Interstitial lung disease: causes, treatment, and prevention.

The interstitial lung diseases (ILD) are a diverse group of lung disorders that involve primarily the parenchyma of the lung. Whether idiopathic or secondary to systemic disorders, inhaling exposures, or drugs, they inflame and scar the interstitium of the lungs and obliterate alveoli and capillary units. The scarring or fibrosis produces restrictive lung impairment while destruction of the alveoli, interstitium, and capillaries results in severe gas exchange abnormalities. Clinically, the ILD present subtly with progressive dyspnea on exertion and a dry cough. Rales or crackles on examination prompt chest radiography that may reveal bilateral infiltrates. These infiltrates are often treated as atypical pneumonias that fail to respond to antimicrobial therapy over weeks to months. Because of this and their infrequent presentation in the primary care setting, the diagnosis of ILD is commonly delayed. This paper highlights the natural history of the ILD in general, gives a broad overview of the pathophysiology in these diseases, and encourages greater awareness for the detection of ILD in primary care.

COPD in VA hospitals.

The Department of Veterans Affairs (VA) Health Care System is the largest integrated single-payer system in the United States. Its primary mission is to provide primary care, specialized care, and related medical and social support services to veterans. Much time and resources are expended on chronic obstructive pulmonary disease, known as COPD, at VA hospitals and clinics, thereby justifying the development of multifaceted strategies to address this problem. This article discusses the special problems of COPD in veterans who use VA facilities. The article also highlights the contributions of the VA to the research, training, and development of clinical practice guidelines for the management of this pervasive disease and presents the challenges that threaten its role in this area.

Pulmonary granulomatous inflammation: From sarcoidosis to tuberculosis.

Granulomatous inflammation of the lung is characterized by the recruitment and organization of activated macrophages and lymphocytes in discrete lesions laced in a network of matrix proteins. These lesions, termed granulomas, represent an important defense mechanism against infectious organisms such as fungi and mycobacteria, but also can be elicited by noninfectious agents. Occasionally, this inflammatory reaction can develop for unknown reasons, causing a systemic illness termed sarcoidosis. The mechanisms involved in granuloma formation in the lung have not been elucidated entirely. However, studies performed in animal models of granuloma formation and in humans suggest important roles for specific soluble mediators (eg, cytokines, chemokines) produced by monocytic cells. If uncontrolled, granulomatous inflammation leads to excessive tissue remodeling, causing fibrosis and/or cavitation as seen in tuberculosis. This review summarizes our current understanding of the factors involved in granuloma formation in the lung with particular attention to their role in sarcoidosis and tuberculosis.